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Cited by 246Axon Guidance and Neuronal SignalingDevelopmental Biology and Gene RegulationNerve injury and regeneration

Vav family GEFs link activated ephs to endocytosis and axon guidance

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Cowan, Christopher W., Shao, Yu Raymond, Sahin, Mustafa, Shamah, Steven M., Lin, Michael Z., Greer, Paul L., Gao, Sizhen, Griffith, Eric C. +2 more·2005·Neuron
DOI 10.1016/j.neuron.2005.03.019
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Abstract

Ephrin signaling through Eph receptor tyrosine kinases can promote attraction or repulsion of axonal growth cones during development. However, the mechanisms that determine whether Eph signaling promotes attraction or repulsion are not known. We show here that the Rho family GEF Vav2 plays a key role in this process. We find that, during axon guidance, ephrin binding to Ephs triggers Vav-dependent endocytosis of the ligand-receptor complex, thus converting an initially adhesive interaction into a repulsive event. In the absence of Vav proteins, ephrin-Eph endocytosis is blocked, leading to defects in growth cone collapse in vitro and significant defects in the ipsilateral retinogeniculate projections in vivo. These findings suggest an important role for Vav family GEFs as regulators of ligand-receptor endocytosis and determinants of repulsive signaling during axon guidance.

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Crossref · 10.1016/j.neuron.2005.03.019

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  • 5xFAD Cass4-/- inhibitory neurons exhibited downregulation of genes and pathways involved in neuronal circuitry.

    “Moreover, we observed a downregulation of genes and pathways involved in neuronal circuitry such as Sv2b , Vav3 , Arhgap24 , Asap2 , Elmo1 , and Nrn1 in 5xFAD Cass4 -/-mice relative to 5xFAD littermate controls (Agrawal et al., 2026; Chan et al., 2020; Cowan et al., 2005; Falace et al., 2024; Hale et al., 2011; Kim et al., 2011; Li et al., 2018; Miyamoto et al., 2020; Pugh et al., 2026; Sauzeau et”

    From Alzheimer’s genetic risk factor CASS4 controls microglial focal adhesion biology and amyloidosis (2026) · cites this paper as Cowan et al., 2005

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Authors
Cowan, C. W., Shao, Y. R., Sahin, M., Shamah, S. M., Lin, M. Z., Greer, P. L., Gao, S., Griffith, E. C., Brugge, J. S., & Greenberg, M. E.
Affiliations
  • Boston Children's Hospital (US)
  • Harvard University (US)
Corresponding author
Greenberg, Michael E.
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2005-04
Volume
46
Issue
2
Pages
205-217
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2005.03.019
OpenAlex
W1974931752
Cited by
246
References
0
Citations by year
2026: 2 · 2025: 8 · 2024: 1 · 2023: 5 · 2022: 9 · 2021: 6 · 2020: 5 · 2019: 7 · 2018: 11 · 2017: 5 · 2016: 8 · 2015: 12 · 2014: 11 · 2013: 15 · 2012: 21
FWCI
7.74
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ns045500-29, 5k08hd001384-02)
  • National Heart, Lung, and Blood Institute (P01HL059561, HL059561)
  • National Institute of Neurological Disorders and Stroke (R01-NS-045500, NS43855)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD18655, K08 HD01384, P30HD018655)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
Keywords
Vav2, Eph receptors, ephrin signaling, axon guidance, endocytosis, receptor-ligand complex, growth cone collapse, retinogeniculate projections, Rho GTPases
MeSH terms
Animals, Endocytosis, Signal Transduction, Mice, Knockout, Microscopy, Confocal, Growth Cones, rho GTP-Binding Proteins, Two-Hybrid System Techniques, Receptors, Eph Family, Ephrins, Mice

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